Diabatic Mechanisms of Higher-Order Harmonic Generation in Solid-State Materials under High-Intensity Electric Fields.

We theoretically investigate mechanisms of higher-order harmonic generation in solid-state materials under a high-intensity ac electric field. A new theoretical framework presented in this Letter holds the legitimacy of Bloch's theorem even under the influence of the high-intensity electric field and provides an exact treatment of the diabatic processes of Bloch electrons. Utilizing this framework, we first discovered that the diabatic processes, namely, ac Zener tunneling and semimetallization of semiconductors, are key factors for nonperturbative mechanisms of HHG. These mechanisms are classified by the field intensity and could be understood by an extended simple man model based on an analogy between tunnel ionization in gaseous media and Zener tunneling in semiconductors. These conclusions would stimulate the universal understanding of HHG mechanisms in both atomic and solid cases.

Novel therapeutic strategy for uterine arteriovenous fistulas: case report.

BACKGROUND: The major presenting symptom of uterine arteriovenous fistulas is massive, torrential vaginal bleeding, the degree of which often leads to a shock state. CASE: A 35-year-old woman, gravida 3, para 2 presented with massive vaginal hemorrhage at the first menstruation six months after delivery. Uterine arteriovenous fistulas were diagnosed by color Doppler ultrasonography (US), dynamic computer tomography (CT), and conventional angiography. The patient underwent hysterectomy after bloodstream decrease by bilateral uterine artery embolization. CONCLUSION: The extent of uterine arteriovenous fistulas was diagnosed by color Doppler US, CT, and pelvic angiography, and this precise evaluation led to an adequate therapeutic strategy for uterine arteriovenous fistulas.

Expression of the inhibitor of DNA-binding (ID)-1 protein as an angiogenic mediator in tumour advancement of uterine cervical cancers.

The ID protein, an inhibitor of basic helix-loop-helix (HLH) transcription factors, has been involved in multiple cellular processes. To investigate the association between tumour advancement and ID expressions of uterine cervical cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction and the histoscore with the localisation of ID-1 was determined by immunohistochemistry and patient survival in 60 patients. ID-1 histoscores and mRNA levels both significantly (P<0.05) increased in uterine cervical cancers according to clinical stage regardless of histopathological type or lymph node metastasis. Furthermore, the 36-month survival rate of the 30 patients with high ID-1 was poor (60%), whereas that of the other 30 patients with low ID-1 was significantly higher (83%). ID-1 histoscores and mRNA levels significantly (P<0.0001) correlated with microvessel counts in uterine cervical cancers. Tumour cells show mostly diffuse to strong cytoplasmic expression of ID-1 and also very faint expression in endothelial cells. Moreover, ID-1 expression not only correlated with microvessel counts but also correlated significantly with histoscore. Therefore, ID-1 might work on tumour advancement through angiogenic activity and is considered to be a candidate for a prognostic indicator in uterine cervical cancers.

Clinical implication of medroxyprogesterone acetate against advanced ovarian carcinoma: a pilot study.

PURPOSE OF INVESTIGATION: The present study was performed to identify the effects of medroxyprogesterone acetate (MPA) plus adjuvant chemotherapy on advanced epithelial ovarian carcinoma (FIGO Stage III/IV). METHODS: A total of 50 patients were enrolled in this study. A relatively low dose of MPA (200 mg/day) after surgery was administered in combination with platinum-based chemotherapy and the treatment was continued for two years. Patients' backgrounds were also analyzed. RESULTS: Relapse-free survival (p < 0.05) and overall survival (p < 0.001) rates in FIGO Stage III/IV ovarian cancer patients with MPA combined chemotherapy were significantly longer than the control group. The effect was more prominent in the higher progesterone receptor expression group. The chemotherapy regimens (cyclophosphamide, doxorubicin and cisplatin vs paraplatin plus cyclophosphamide or paclitaxel) did not affect prognosis. CONCLUSION: MPA with platinum-based chemotherapy as an adjuvant therapy might improve the prognosis in FIGO Stage III/IV epithelial ovarian cancer cases. A randomized controlled study is still needed for further analyses.

Coexpression of EphB4 and ephrinB2 in tumour advancement of ovarian cancers.

EphB4 and ephrinB2 expressions in ovarian cancers were studied to analyse EphB4/ephrinB2 functions against clinical backgrounds. EphB4 and ephrinB2 were dominantly localised in ovarian cancer cells of all cases studied. Both the histoscores and mRNA levels of EphB4 and ephrinB2 significantly increased with clinical stages (I

Role of protease activated receptor-2 in tumor advancement of ovarian cancers.

BACKGROUND: Protease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis with angiogenesis in various tumors. This prompted us to study the role of PAR-2 in tumor advancement of ovarian cancers. MATERIALS AND METHODS: Forty-eight patients underwent surgery for ovarian cancers. In ovarian cancers, PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. Patient prognosis was analysed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD31 and factor VIII-related antigen and the rate of cell proliferation was determined by immunohistochemistry for Ki67. RESULTS: Immunohistochemical staining revealed distribution of PAR-2, dominantly in cancer cells and faintly in stromal cells of the tumor. PAR-2 histoscores in cancer cells and mRNA levels both significantly increased in ovarian cancers with clinical stages (I < II < III < IV, P < 0.05), regardless of histopathological type. The 36-month survival rate of 24 patients with high PAR-2 was poor (58%), while that of the other 24 patients with low PAR-2 was significantly higher (83%). There were significant correlations between PAR-2 histoscores in cancer cells and mRNA levels with microvessel counts and with the rate of cell proliferation in ovarian cancers. CONCLUSIONS: PAR-2 was up-regulated during ovarian cancer progression. Therefore, PAR-2 might work on tumor advancement of ovarian cancers via angiogenic activity and is considered to be a novel prognostic indicator in ovarian cancers.

Effects of selective estrogen receptor modulators and genistein on the expression of ERalpha/beta and COX-1/2 in ovarectomized mouse uteri.

This study was performed to examine the effects of selective estrogen receptor modulators [tamoxifen (TAM) and toremifene (TOR)] and pure anti-estrogen, ICI-182780 (ICI, Faslodex) and soybean isoflavone, genistein (GE) on the expression of estrogen-stimulated c-fos/jun, ERalpha/beta and COX-1/2 in the uteri of ovarectomized mice. TAM, TOR, ICI and GE treatment significantly decreased the levels of estradiol (E2)-induced c-fos. ICI and GE treatment significantly decreased the levels of E2-induced c-jun and ERalpha expressions. High doses of TOR treatment significantly increased the E2-induced ERbeta expression. In contrast, ICI and GE treatment significantly decreased the levels of E,-induced COX-2 expression, thus suggesting that TOR and GE might prevent E2-related endometrial carcinogenesis.

Pseudomyxoma peritonei and mucinous pyometral fluid arising from an ovarian borderline mucinous tumor: case report.

An extremely rare case of a pseudomyxoma peritonei (PMP) and mucinous pyometral fluid, possibly arising from an ovarian borderline mucinous tumor is reported. A 68-year-old Japanese patient received an expolatory laparatomy under a working diagnosis of a PMP, left ovarian cystic tumor and an umbilical hernia. Surgery and platinum-based chemotherapy induced a 15-month disease-free condition.

Expression of IP-10 related to angiogenesis in uterine cervical cancers.

Angiogenesis is essential for development, growth and advancement of solid tumours. Interferon-gamma-inducible protein 10 (IP-10) regulates lymphocyte chemotaxis, mediates vascular pericyte proliferation and acts as an angiostatic agent, thus inhibiting tumour growth. This prompted us to study the clinical implications of IP-10 expression related to angiogenesis in uterine cervical cancers. The levels of IP-10 decreased with advancement, and the prognosis of the 30 patients with low IP-10 expression in uterine cervical cancers was poor (66%), whereas the 24-month survival rate of the other patients with high IP-10 expression was 90%. Furthermore, IP-10 levels significantly reverse-correlated with vascular endothelial growth factor (VEGF) levels in uterine cervical cancers. Interferon-gamma-inducible protein 10 might work on suppression of angiogenesis associated with VEGF in advancement, and can be recognised as a prognostic indicator. Furthermore, IP-10 activation might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced cervical cancers.

Primary endodermal sinus tumor of the vulva in a 52-year-old woman with long-term survival: a case report.

A postmenopausal 52-year-old Japanese woman with a 5-month history of a right labial tumor was referred to the Department of Obstetrics and Gynecology. The resected tumor had been diagnosed as a primary endodermal sinus tumor of the vulva with pT2N0M0 in 2001. Six courses of adjuvant chemotherapy using bleomycin, etoposide and cisplatin were administered. The patient was free of recurrence or metastasis 67 months after the initial treatment.

Primary lymphoma of the uterine corpus: an unusual location for a common disease--case report.

A case of a primary uterine corpus lymphoma in a 75-year-old woman is described. Immunohistochemical studies showed diffuse large B-cell type one. Primary lymphoma of the uterine corpus is considered to be an unusual location for a common disease.

Overexpression of ephrinB2 and EphB4 in tumor advancement of uterine endometrial cancers.

BACKGROUND: The ligand ephrinB2 and the corresponding receptor EphB4 contribute to tumor growth in various human tumors. This prompted us to study the expression and localization of ephrinB2 and EphB4 in uterine endometrial cancers to analyze the ephrinB2/EphB4 functions against clinical backgrounds. MATERIALS AND METHODS: We carried out immunohistochemistry and real-time RT-PCR to determine the histoscores and messenger RNA (mRNA) levels of ephrinB2 and EphB4, respectively, in 68 uterine endometrial cancers and 16 normal endometrium tissue samples. Patient prognoses were analyzed with a 60-month survival rate. RESULTS: The localization of ephrinB2 and EphB4 was dominantly in the cancer cells of uterine endometrial cancer of all cases given. EphrinB2 and EphB4 histoscores were highly correlated with ephrinB2 and EphB4 mRNA levels, respectively (r = 0.864 and r = 0.615, P < 0.01). Both the histoscores and mRNA levels of ephrinB2 and EphB4 significantly increased with clinical stages (I < II < III, P < 0.01), dedifferentiation (G(1) < G(2) < G(3), P < 0.01) and myometrial invasion (A < B < C, P < 0.01 for ephrinB2 and P < 0.05 for EphB4) in uterine endometrial cancers. The 60-month survival rates of the 34 patients with high ephrinB2 and EphB4 expression were poor (59% and 62% respectively), while for the other 34 patients with low ephrinB2 and EphB4 expression, they were significantly higher (85% and 82%, respectively). CONCLUSIONS: EphrinB2 and EphB4 were overexpressed during the tumor advancement as dedifferentiation and myometrial invasion. Therefore, ephrinB2/EphB4 might work on tumor advancement and may be recognized as a novel prognostic indicator for uterine endometrial cancers.

Gi protein-mediated translocation of serine/threonine phosphatase to the plasma membrane and apoptosis of ovarian cancer cell in response to gonadotropin-releasing hormone antagonist cetrorelix.

Serine/threonine protein phosphatase 2A (PP2A), a crucial enzyme in apoptosis control, has been demonstrated within the plasma membrane as well as in the soluble fraction. This study aimed to examine hormonal translocation of PP2A to the plasma membrane in gonadotropin-releasing hormone (GnRH)-responsive ovarian cancer cells. Apoptosis of ovarian cancer cell lines Caov-3 and SK-Ov-3 was quantified by nuclear morphology after staining with Hoechst 33342 dye. PP2A protein and activity in plasma membrane were assessed by immunohistochemical staining with PP2A-specific antibodies and by the measurement of the dephosphorylation of phosphopeptide highly selective for the PP2A, respectively. Incubation for 48 h with a GnRH antagonist cetrorelix caused parallel increases in the percentage of cells undergoing apoptosis and the membrane-associated PP2A activity; half-maximal effects occurred with 5 nmol/l cetrorelix. PP2A protein was also localised to the plasma membrane when the cell lines were exposed to cetrorelix. Pretreatment of the cells with pertussis toxin, but not cholera toxin, completely inhibited cetrorelix-stimulated apoptotic cell death and PP2A redistribution. These findings demonstrate that translocation of PP2A to plasma membrane is closely coupled to the onset of apoptosis in ovarian cancer cells exposed to GnRH antagonist. These GnRH-induced cellular events may be mediated through pertussis toxin-sensitive Gi protein-linked GnRH receptor.

Effects of dioxin and nutrition on cellular proliferation and dioxin- and estrogen-linked genes in ovarian cancer cell lines.

This study was undertaken to examine the effects of dioxin (TCDD) and nutrition on cellular proliferation and dioxin- and estrogen-linked gene expression in ovarian cancer cell lines. Caov-3 and SK-OV-3 cells were incubated in a medium supplemented with 0.5-10% fetal bovine serum (FBS). Cell proliferation was assayed with an MTT assay. Dioxin- and estrogen-linked genes (AhR, ERalpha, ERbeta, CYP1A1 and ARNT) expressed were determined with the RT-PCR method. Caov-3 cells, but not SK-OV-3 cells, were proliferated with TCDD alone with increased AhR and ERa mRNA expressions when incubated in the low FBS concentration. CYP1A1 and ARNT mRNA expressions of SK-OV-3, but not that of Caov-3, were suppressed in the low FBS (under 1.0%) concentration. In the low FBS concentration medium with dioxin, AhR and ERa expression were increased with the proliferation of Caov-3 cells; CYP1A1 and ARNT were stable. Each ovarian cancer cell line may have its own distinct responsiveness to dioxin depending on the nutritional state.

Outcome of fertility-preserving treatment in young women with endometrial carcinomas.

OBJECTIVE: To evaluate the outcome of conservative treatment of young women with endometrial cancer. DESIGN: Observational study. SETTING: Gifu University Hospital, Japan from 1988 to 2002. POPULATION: Twelve women with endometrial cancer, FIGO IA estimated by MRI under 35 years. METHODS: Patients were treated with medroxyprogestreone acetate (400-600 mg/day) for 6-10 months, with endometrial curettage performed every four weeks. MAIN OUTCOME MEASURES: Response to therapy, pregnancies and reoccurrence of disease during follow up over a 30-month period. RESULTS: All cases had pathological complete remissions within 6-10 months. Seven of 10 wishing to have babies conceived, and five of them were delivered of full-term babies. Eight of nine cases receiving long term follow up (over 30 months) developed recurrent disease, with four opting for hysterectomy. No patient developed distant metastases or had disease-related death. CONCLUSION: Conservative therapy is feasible in carefully selected young women with endometrial cancer. Recurrence rates were high during long term observation even after pathological complete remissions. Therefore, close follow up is recommended.

Clinical implications of expression of cyclooxygenase-2 related to angiogenesis in uterine endometrial cancers.

BACKGROUND: Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (cox)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of cox-2 expression and angiogenesis in uterine endometrial cancers. PATIENTS AND METHODS: Fifty patients underwent curative resection for uterine endometrial cancers. In uterine endometrial cancers, cox-2 levels were determined by enzyme immunoassay, and the localization and counts of microvessels were determined by immunohistochemistry. RESULTS: There was a significant correlation between microvessel counts and cox-2 levels in uterine endometrial cancers. Cox-2 localized in the cancer cells, but not in the stromal cells of uterine endometrial cancer tissues. Cox-2 levels decreased with the advancement. Furthermore, cox-2 levels significantly correlated with VEGF levels in uterine endometrial cancers. CONCLUSIONS: VEGF associated with cox-2 might work on angiogenesis at an early status in growth. Therefore, long-term administration of cox-2 inhibitors might be effective in the suppression of recurrent initiation of uterine endometrial cancers after curative resection.

Augmentation of leptin and hypoxia-inducible factor 1alpha mRNAs in the pre-eclamptic placenta.

The placenta is a major source of leptin in the fetomaternal circulation, although its physiological role remains to be clarified. Leptin in the fetomaternal circulation is proposed to be a marker of acute stress in the fetus, and the fetus suffering from pre-eclampsia would be under chronic stress. In 16 pre-eclamptic placentas, the expressions of leptin, hypoxia-inducible factor 1alpha (HIF1alpha) and leptin receptor mRNAs were analyzed by semi-quantitative reverse-transcriptase-polymerase chain reaction and compared with clinical data. The co-expressions of leptin and the isoforms of the leptin receptor were observed in all the pre-eclamptic placentas. Leptin mRNA was significantly augmented in the pre-eclamptic placentas, although the level in fetal plasma was not high. The level of the expression of leptin mRNA was correlated with the placental HIF1alpha mRNA level and fetal body weight, but not with the levels of the leptin receptor isoforms in the pre-eclamptic placentas. This observation may suggest that autocrine/paracrine regulation of leptin exists in the human placenta and is upregulated in the pre-eclamptic placenta.

Clinical implication of expression of vascular endothelial growth factor-C in metastatic lymph nodes of uterine cervical cancers.

Vascular endothelial cell growth factor (VEGF)-C levels were significantly (P<0.05) increased in 24 out of 40 metastatic lymph node lesions of uterine cervical cancers. The prognosis of the 24 patients with increased VEGF-C level in metastatic lymph node lesions was poor and the 24-month survival rate was 38%, while the rate of the 16 patients with no change in VEGF-C level in metastatic lymph node lesions was 81%. There was a significant (P<0.01) difference in the 24-month survival rates between the two groups. This is novel, direct evidence that VEGF-C might contribute to the aggressive lymphangitic metastasis in uterine cervical cancers, and that the increase in VEGF-C level from primary tumour to metastatic lymph node might be a prognostic indicator.

Soybean isoflavones inhibit estrogen-stimulated gene expression in mouse uteri.

This study was performed to examine the inhibitory effects of soybean isoflavones on estrogen-stimulated gene expression of the uteri in ovarectomized mice. Especially when compared with the inhibitory effect of genistein and daidzein as aglycosides described in our previous report, subcutaneous administration of the glycoside genistin significantly decreased the levels of estradiol-17beta (E2)-induced expressions of c-jun, interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha mRNAs (p < 0.005, p < 0.05 and p < 0.05, respectively) and seemingly proteins in the mice uteri, whereas the glycoside daidzin weakly inhibited E2-stimulated expressions of c-fos and IL-1alpha. Both genistin and daidzin seemed to have a weaker inhibitory effect than that of genistein and daidzein on the expression of estrogen-stimulated genes. It is suggested that those glycosides are naturally derived and generally absorbed from plant foods and might prevent E2-related endometrial carcinogenesis.

Clinical implications of insulin-like growth factors through the presence of their binding proteins and receptors expressed in gynecological cancers.

Since insulin-like growth factors (IGFs) are known to play critical roles in the development of cancers, we examined the expression of the mRNA and protein of IGF-binding protein (IGFBP) and cognate receptors to assess their possible involvement in gynecological malignancy. The specimens were obtained from 46 endometrial, 32 cervical, and 20 ovarian cancers, and 28 normal endometrium. In endometrial cancers, IGFBP-1, -2, -3 and IGF-1 receptor (IGF-1R) mRNAs were detected in 8.7, 89.1, 95.6, and 91.3% of tumors, respectively, and the corresponding proteins in 54.3, 54.3, 95.6, and 91.3% of tumors, respectively. Clinical staging was significantly related to the expression of IGFBP-1 and -2 proteins. In ovarian cancers, their mRNAs were detected in 10.0, 90.0, 95.0, and 100.0%, and proteins in 15.9, 50.0, 90.0, and 80.0%. In cervical cancers, their mRNAs were detected in 6.3, 90.6, 96.8, and 87.5%, and proteins in 44.4, 18.8, 84.4, and 87.5%. IGF-1R was highly expressed in all specimens. The abnormally balanced co-expression of IGFBPs and high levels of IGF-R in gynecological cancers suggest that IGF signals might be involved in the growth of these tumors.